2012 Grants - Ran

Qitao Ran, Ph.D.
University of Texas Health Science Center at San Antonio
San Antonio, Texas

2012 Investigator-Initiated Research Grant

Mitochondria are specialized components of cells that convert energy sources into forms that the cells can use. During this process and other cellular processes, chemicals are generated that can cause oxidation (the loss of electrons or gain of oxygen) and damage to proteins in mitochondria as well as other parts of the cells. Some of this damage results in the attachment of chemical groups, such as glutathione (a simple molecule that is produced naturally in the body, and is a combination of cysteine, glycine and glutamine) to proteins (glutathionylation). There is evidence that nerve cells in the brains of people who have Alzheimer's disease have high levels of glutathionylated proteins.

Glutaredoxin 2 is an enzyme that reverses glutathionylation of proteins in the mitochondria. Qitao Ran, Ph.D., and colleagues used genetic engineering techniques to create a strain of mice that have high levels of glutaredoxin 2. These mice have reduced levels of glutathionylated proteins in their mitochondria.

Dr. Ran and colleagues have proposed to test whether such mice are more resistant to the Alzheimer's disease process. They plan to perform further genetic engineering to create a strain of mice that have genes leading to an Alzheimer's-like condition, as well as genes causing increased levels of glutaredoxin 2. This model will allow the researchers to determine if high glutaredoxin 2 levels can prevent nerve cell damage caused by Alzheimer's-related genes. These studies will help determine if drugs to activate glutaredoxin 2 could be viable treatments to prevent or slow the progression of Alzheimer's disease.